This research project is a part of an ongoing research program aimed at elucidating the biochemical basis of the psychopharmacological effects produced by some of the serotonin depletors in cerebral function, namely p-chlorophenylalanine (p-CP) and p-chloroamphetamine (p-CA). These compounds are important psychopharmacological agents, influencing such functions as sleep, pain, sexuality, and gross and consummatory behavior in rats and human beings. The appearances of changes in the above events is largely related to their effects on serotonin metabolism. p-CA, through its being neurotoxic to the serotonergic system, involving nuclei in raphe and striatum, and p-CP, by being a specific, selective, irreversible inactivator of 5-hydroxytryptophan synthesis, exert their powerful psychopharmacological effects. In view of our investigations, it is our thesis that inactivation of tryptophan and phenylalanine hydroxylases by p-CP results from the changes in these enzymes at or near their active center. Evidence that this occurred via their protein synthesis was obtained. Inactivation of these hydroxylases was suppressed in animals pretreated with inhibitors of protein synthesis prior to administration of p-CP in vivo. Additionally, the effect of these drugs on cerebral synthesis and profile of tetrahydrobiopterin, cofactor of tryptophan and tyrosine hydroxylases, and on the conversion of tryptophan to kynurenine in the brain is under investigation.